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Journal of Neurosurgical Sciences 2016 Jun 15


lingua: Inglese

MHC harnessing and lymphocytic recruitment: a new tool for GBM immunotherapy

Or COHEN-INBAR 1-4, Yoram REITER 5, Menashe ZAAROOR 1-3

1 Department of Neurological Surgery, Rambam Health Care Center, Haifa Israel; 2 Molecular Immunology Laboratory, Technion Israel Institute of Technology, Haifa Israel; 3 Faculty of Medicine, Technion Israel Institute of Technology, Haifa Israel; 4 Department of Neurological Surgery and Gamma-Knife Radiosurgical Center, University of Virginia Health Care Center, USA; 5 Laboratory of Molecular Immunology, Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel


Glioblastoma Multiforme (GBM) is the most common malignant primary brain neoplasm, notorious for being able to evade and suppress the immune-system. We present a new immunotherapeutic approach that can potentially overcome or circumvent many of the GBM laden obstacles for an efficient anti-tumor immune response. In this molecular construct, a soluble Major-Histocompatibility Complex (MHC), presenting an immunogenic peptide is directed towards GBM cells. This soluble complex is known to be able to activate relevant cytotoxic T-lymphocyte (CTL’s) populations, mounting an effective local immune response. The chimeric protein consists of a targeting domain, a function that can be fulfilled by an antibody or other small molecule that binds tumor associated antigens, and an effector domain. A single chain MHC directly linked to an immunogenic CMV derived peptide (phosphoprotein 65) can be used as such an effector domain. Targeting MHC complexes to the tumor enables to recruit different lymphocyte populations using MHC-molecules bearing a single, highly antigenic peptide derived from immunogenic T cell epitopes. Moreover, the recruited potent memory CTL’s at the tumor’s milieu may prove resistant to the previously described local immunosuppressive environment, and may enables the shift to TH1 cytokine profile resulting in specific massive tumor destruction.

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